Fecal Bile Acids, Fecal Short Chain Fatty Acids and the Intestinal Microbiota in Patients With Irritable Bowel Syndrome (IBS) and Control Volunteers: Diet Challenge
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Total fecal bile acids
Study Overview
Brief Summary
The study will investigate the relationship between fecal bile acids, short-chain fatty acids (SCFAs), and the gut microbiota in irritable bowel syndrome (IBS). The central hypothesis of this study is that specific shifts in the GI microbiome composition correlate with altered colonic SCFAs and BAs and contribute to IBS symptoms. Primary aims include: (a) identifying GI microbiome signatures in IBS subtypes (IBS-C and IBS-D) and matched controls, and test if microbiome signatures in these groups correlate with fecal SCFAs and bacterial fermentation of an indigestible carbohydrate (inulin) after a dietary challenge (fecal inulin), and (b) determining if GI microbiome signatures in IBS subtypes and controls correlate with fecal BAs or markers of SCFA production (fecal SCFAs or inulin) and test if BAs correlate with fecal SCFAs or inulin.
The target population is adults ages 18-65 years meeting Rome IV criteria for IBS (both diarrhea- and constipation-predominant, IBS-D and IBS-C) and asymptomatic controls. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100 g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis.
Detailed Description
During the study:
Screening/Visit 1
- Participants will be asked to read and sign this informed consent after all questions about the study have been answered to satisfaction.
- This is a screening visit, and we may determine that a participant is ineligible to continue to participate in the study.
- The study team will collect medication and medical history.
- A physical exam will be performed by the physician. Vital signs and body measurements will be collected.
- Participants will be provided with a take-home lasagna meal (vegetarian and non-vegetarian option) and dessert.
- Participants will receive a stool collection kit and instructions for the collection, storage, and transportation of stool.
- Instructions will be provided for a low fiber, high fat diet for Days 2-4.
- Participants will be asked to complete diet recall using the ASA24 and a bowel pattern diary to record bowel symptoms over the course of the study.
- IBS participants will complete the irritable bowel syndrome severity scoring system questionnaires (IBS-SSS).
Day 2-4 (at home):
- Participants will record stool symptoms and patterns in a diary daily.
- Participants will be instructed to consume a low fiber diet (maximum one piece of fruit and 100 g of vegetables a day, and white flour instead of whole grain products), avoid alcohol, and start a 4-day 100 g fat diet.
- On the evening before Day 5, participants will be instructed to collect a stool sample at home and return during Visit 2.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age 18-75
- •Individuals with irritable bowel syndrome (IBS)
- •Healthy volunteers (healthy controls) with no prior history of gastrointestinal (GI) disease or symptoms
- •No dietary restrictions other than vegetarian
Exclusion Criteria
- •Inflammatory bowel disease, celiac disease, or certain types of abdominal cancer, as well as those with thyroid or liver issues
- •Abdominal surgery or abdominal radiation within 6 months of study participation, with an exception for C-section or gallbladder removal
- •Use of any prescription, over the counter, or herbal medications known to affect gastrointestinal function or study interpretation, such as opioids, inflammatory drugs or certain antidepressants, within 6 months prior to study participation for healthy volunteers, or within 2 days of study participation for participants with IBS.
- •An exception will be permitted for limited use of stable low doses of antidepressants for individuals who have been taking them for a period greater than one month.
- •Rescue medication such as Bisacodyl (dulcolax) to relieve severe constipation and allow for stool collection will be permitted when needed.
- •Use of Ozempic and Ozempic-type medications
- •Pregnant or breastfeeding women
- •Antibiotic use within 3 months of study participation
- •Use of prebiotics or probiotics within the 2 weeks before the study initiation
- •Regular tobacco use within the past 6 months
Arms & Interventions
Irritable Bowel Syndrome Patients with Constipation (IBS-C)
Patients with irritable bowel syndrome (IBS) with constipation, ages 18-65 years fulfilling Rome IV criteria for IBS.
Intervention: Inulin (Dietary Supplement)
Irritable Bowel Syndrome Patients with Diarrhea (IBS-D)
Patients with irritable bowel syndrome (IBS) with diarrhea, ages 18-65 years fulfilling Rome IV criteria for IBS.
Intervention: Inulin (Dietary Supplement)
Healthy volunteers
Adults ages 18-65 years with no prior history of gastrointestinal diseases or symptoms.
Intervention: Inulin (Dietary Supplement)
Outcomes
Primary Outcomes
Total fecal bile acids
Time Frame: 48 hours
Stool samples will be collected over 2 days for measurement of fecal bile acids (µmol/48h) by high performance liquid chromatography-mass spectometry.
Total fecal short chain fatty acids
Time Frame: 48 hours
Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
Individual fecal short chain fatty acids
Time Frame: 48 hours
Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
Fecal microbial population
Time Frame: 48 hours
Stool samples will be be collected from participants for nucleic acid extraction, 16S allele PCR and sequencing to measure microbial communities and profiles of specimens
Fecal inulin
Time Frame: 48 hours
Fecal inulin content will be measured using short acid hydrolysis and high-performance liquid chromatography
Secondary Outcomes
- Stool characteristics(4 days)
- Percent primary fecal bile acids(48 hours)
Investigators
Andrea S. Shin, MD
Associate Professor
University of California, Los Angeles